Alpha amino substituted methylenemalononitriles



Unite States 3,057,864 ALPHA AMINO SUBSTHTUTED METHYLENE- MALONONITRILES Alexander T. Shulgin, Berkeley, Calif., assignor to The Dow Chemical Company, Midland, Mich, a corporation of Delaware No Drawing. Filed Aug. 28, 1959, Ser. No. 836,581 4 Claims. (Cl. 260-247) wherein the free valence is occupied by a nitrogen atom, the said occupying nitrogen being a member of a heterocyclic group having a total of not more than two ringnitrogen atoms, free of imino nitrogen atoms and having from three to six members in the ring and not more than one ring substituent additional to the methylene malononitrile group, each such additional substituent being a lower alkyl group; each valence of said occupying nitrogen atom being attached to a separate carbon atom. The term lower alkyl is used throughout the present specification and claims to designate an alkyl group containing from 1 to 5 carbon atoms, inclusive. In View of the present definition, it is apparent that compounds representative of the present invention include the following:

Ethyleniminomethylenemalononitrile T1-imethyleniminomethylenemalononitrile HzCOH2 CN H /NG=O\ HQC-CH3 CN Pyrrolidinyhnethylenemalononitrile Hg Hz 0-0 C-O ON Piperidinylmethylenemalononitrile CHTCH; ON

ON HaC-N atet ice

N -tert-butylpiperazinylmethylenernalononitrile It will be apparent from the foregoing definition that when the heterocyclic group contains a second nitrogen atom, such second nitrogen atom is invariably a tertiary, that is to say, a fully substituted nitrogen atom having a lower alkyl group as substituent thereupon. When the only nitrogen atom in the heterocyclic group is the nitrogen atom which is attached to the methylenemalonitrile group, such lower alkyl substituent, if present, may be present in any available location upon the heterocyclic group.

These new compounds are crystalline solids somewhat soluble in many common organic solvents and of very low solubility in ethanol and in water. They are useful as parasiticides and are adapted to be employed for the control of many household pests such as insects and agricultural parasites such as weeds and fungus diseases.

The new compounds may be prepared by causing a lower alkoxymethylenemalononitrile to react With a heterocyclic secondary amine having a total of not more than 2 ring nitrogen atoms one of which is an amino nitrogen atom, and having from 3 to 6 members in the ring and not more than one ring substituent, each such substituent being a lower alkyl group; the imino nitrogen being joined in the ring by the presence, upon each ring valence bond thereof, of a separate carbon atom which is also a member of the ring. Representative heterocyclic secondary amines include ethylenimine, trimethylenimine, pyrrolidine, piperidine, morpholine, thiamorpholine, N-lower alkyl piperazine, and the like. Representative lower alkoxymethylenemalononitriles include ethoxymethylenemalononitrile, methoxymethylenemalononitrile, isopropoxymethylenemalononitrile, 3,3- dimethylpropoxymethylenemalononitrile, n-propoxymethylenemalononitrile. In the present specification and claims, the term lower alkoxy is used to designate an alkoxy group containing from 1 to 5 carbon atoms, inclusive.

In carrying out the reaction, the lower alkoxy methylenemalononitrile is intimately contacted with a heterocyclic secondary amine of the sort hereinbefore defined. Preferably, the contacting is carried out in an inert solvent which may conveniently be a lower alkanol such as methanol, or ethanol. The reaction is exothermic and initiates readily at temperatures from 0 C. to 50 C.; therefore, the contacting of the reactants is conveniently carried out initially within such temperature range. Heat evolved from the reaction raises the temperature of the resulting reaction mixture, which may conveniently be limited by the boiling temperature of the reaction solvent, by regulating the rate of contacting of the reactants, by external cooling, and the like. The desired products prepared in the present method are stable under temperatures at least somewhat greater than the melting temperature of the said product, at least to temperatures such as ISO- C. The reaction by which the present products are obtained takes place between equimolecular proportions of the heterocyclic secondary amine and the lower alkoxymethylenemalononitrile reactant. However, the reactants may be employed in any proportions. If

employed proportions of reactants differ from equimolecular proportions, in general the reactant in excess thereof will appear as an impurity in, and may be removed from, the resulting product.

Upon completion of the reaction, which is easily recognized by the cessation of evolution of further heat of reaction, the reaction mixture may be cooled to a temperature between room temperature and C., whereupon the desired product usually separates by crystallizing from the reaction mixture. Alternatively, the reaction mixture may be warmed under subatmospheric or atmospheric pressure to vaporize and remove reaction solvent as well as lower alkanol by-product of reaction, to obtain the desired product. When the desired product contains, as impurity, unreacted starting material such material may be removed by washing with portions of a lower aikanol such as ethanol. The resulting product may be further purified by conventional techniques such as by washing with further portions of lower alkanol, and recrystallization from various organic solvents.

The following examples merely illustrate the present invention but are not to be construed as limiting it.

EXAMPLE 1 Piperidinylmethylenemalononitrile A solution of 2.8 grams (0.033 mole) piperidine in milliliters ethanol was added as a single portion to a solution of 4.1 grams (0.034 mole) of ethoxymethylenemalononitrile in milliliters of ethanol warmed to approximately 40 C. A reaction resulted with the immediate evolution of heat, as the resulting reaction mixture became darker in color. The reaction mixture achieved an upper limit temperature of somewhat less than 80 C. The reaction mixture was then chilled over an ice bath for about 4 hours, during which time the desired product separated out of the reaction mixture as crystals, which were removed by filtration and recrystallized from further ethanol. As a result of these operations there was obtained a piperidinylmethylenemalononitrile product as a tan, crystalline solid melting at 90- 92 C., and having a nitrogen content, by analysis, of 25 .54 weight percent as compared with a theoretical value of 26.07 percent.

EXAMPLE 2 l -Pyrr0lidinylmethylenemalononitrile In procedures exactly like the foregoing except that the employed heterocyclic reactant was pyrrolidine there was prepared a l-pyrrolidinylmethylenemalononitrile product as a light tan crystalline solid melting at 88-90 C.

EXAMPLE 3 M arpholinylmethylenemalononitrile The present example was carried out in all respects in the same manner as was Example 1 except that the employed heterocyclic reactant was morpholine. As a result of these operations there was obtained a morpholinylmethylenemalononitrile product as tan crystals melting at 148-150 C.

When the same preparation is carried out except that there is employed isopropoxymethylenemalononitrile in an amount equimolecular with the employed morpholine there is obtained the same morpholinylmethylenemalononitrile product together with isopropanol of reaction.

In preparations similar to the foregoing the following products are obtained:

Ethyleniminomethylenemalononitrile, from the reaction of ethylenimine (boiling at 5657 C.) and ethoxymethylenemalononitrile. Ethylenirninomethylenemalononitrile has a molecular weight of 119.13.

Trimethyleniminomethylenemalononitrile, from the reaction of azetidine (boiling at 6669 C.) and 3,3-dimethylpropoxymethylenemalononitrile. Trimethylenaminomethylenemalononitrile has a molecular weight of 133.2.

Thiamorpholinylmethylenemalononitrile, from the reaction of thiamorpholine and ethoxymethylenemalononitrile. Thiamorpholinylmethylenemalononitrile has a molecular weight of 179.2. The starting thiamorpholine reactant may be prepared in the manner set forth in the Journal of the American Chemical Society, vol. 76 (June 1954), page 2902.

N-methylpiperazinyhnethylenemalononitrile, from the reaction of N-methylpiperazine and methoxymethylenemalononitrile. N-methylpiperazinylmethylenemalononitrile has amolecular weight of 176.2.

N n pentylpiperazinylmethylenemalononitrile, from the reaction of N-n-pentylpiperazine and n-propoxymethylenemalononitrile. N n pentylpiperazinylmethylenemalononitrile has a molecular weight of 232.33.

N tert butylpiperazinylmethylenemalononitrile, from the reaction of N-tert-butylpiperazine and ethoxymethylenemalononitrile. N tert butylpiperazinylmethylenemalononitrile has a molecular weight of 218.3.

The N-loweralkylpiperazines to be employed as reactants according to the present invention may be prepared in the general method set forth in the Journal of the Pharmaceutical Society of Japan, vol. 74, pages1049- 51 (1954).

The new monocyclic N-heterocyclicmethylenemalononitriles of the present invention have been found to be useful as parasiticides and are adapted to be employed for the control of many pests. For such use, the products may be dispersed on inert finely divided solids and employed as dusts. Also, such mixtures may be dispersed in water with the aid of a wetting agent and the resulting aqueous suspensions used as sprays. In other procedures, the products may be employed in oil, as oiI-in-water emulsions, or water dispersions with or without the aid of dispersing or emulsifying agents. In a representative operation, the application as a thorough wetting spray to young tomato plants of a composition containing piperidinylmethylenemalononitrile at the rate of one half pound per hundred gallons of ultimate composition afforded commercially satisfactory protection against subsequent innoculation with viable spores of the fungus Alternaria solani whereas plants similarly innoculated with the fungus but without protection from the present compound were uniformly and heavily infested. Similar results were obtained when employing, as sole toxicant, at the same rate, the compound morpholinylmethylenemalononitrile. Similarly, the compound pyrrolidinylmethylenemalononitrile at the rate of one half pound per hundred gallons afforded substantial protection against subsequent innoculation with the spores of, on tomato plants, Alternaria solani; and on young wheat plants, Puccinia graminis tritici.

I claim:

1. A monocyclic N-heterocyclic methylenemalononitrile having a structure corresponding to the formula ON wherein the free valence is occupied by a nitrogen atom, the said occupying nitrogen atom having each of its two other valences attached to a separate carbon atom and being therewith a component of a saturated heterocycle free from imino nitrogen and having a total of from 3 to 6, inclusive, ring atoms of which the said occupying nitrogen is in the number 1 position; when the said heterocycle contains from 3 to 5, inclusive, ring atoms the ring comprises one trivalent nitrogen atom, all other ring atoms being carbon atoms; and when the said heterocycle contains 6 atoms, the atom in the number 4 position is selected from carbon, trivalent nitrogen, oxygen, and sulfur, all ring atoms other than those numbered 1 and 4 being carbon atoms; said heterocycle having up to 1 lower alkyl substituent additional to the methylenemalononitrile group.

5 6 2. Pyrrolidinylmethylenemalononitri-le corresponding 4. Morpholinylmethylenemalononitrile corresponding to the formula to the formula GET-0H2 ON Hue-CH2 0N H H 0 N-O=O N-O=O\ 5 H2 -0, 0N ON References Cited in the file of this patent 3. Piperidinylmethylenemalononitrile corresponding to UNITED STATES PATENTS the formula H Hz 10 2,425,693 Cook et a1. Aug. 12, 1947 /0-0\ H /CN 2,883,368 Middleton Apr. 21, 1959 E20 NC=O OTHER REFERENCES \C-O/ CN Price et aL: Journal of the American Chemical Society,

15 vol. 68, page 1249 (1946). 

1. A MONOCYCLIC N-HETEROCYCLIC METHYLENEMALONONITRILE HAVING A STRUCTURE CORRESPONDING TO THE FROMULA 